The research plan is to investigate bacterial genes which contribute to E. coli invasion of the blood brain barrier. The goals of this application are to clone, sequence and determine the functional significance of these genes. This application is integral to the candidate's research development and long term goals, of pursuing a career in academic infectious diseases, by affording the opportunity for continued intensive and protected research. Most cases of bacterial meningitis in newborns and children develop as a result of hematogenous spread; in the neonatal period, K1 E. coli are the most common gram negative pathogens responsible for meningitis. The poor outcomes seen in this disease underscore our incomplete knowledge of the pathogenesis and pathophysiology of E. coli meningitis, including how circulating bacteria enter the central nervous system. The overall aim of this research is to enhance our knowledge of the determinants of E. coli which allow it to cross the blood-brain barrier (BBB), specifically the genes and proteins which mediate invasion of brain microvessel endothelial cells (BMEC).